PROJECT SUMMARY End stage renal disease affects millions of Americans and while manageable in its early phases through dialysis, the only treatment is kidney transplantation. Podocytes have been implicated in many kidney diseases and their structural role in the filtration barrier is thought to be a dynamic process by which the podocyte actively reorganizes its actin cytoskeleton. The goal of this project is to combine high-content image analysis with a novel nanotechnology platform to understand how podocytes retain their structural integrity against injury, and use this system to study how a major cell signaling pathway operates in the context of the glomerulus. Our novel research platform comprises spatially-specific microengineered 3-D surfaces that can induce the formation of cell-cell junctions in podocytes. Our platform allows the study of podocyte biomechanics along with other biochemical characteristics simultaneously all in a physiologically relevant microenvironment. Hence, the project is transformative in two ways: first by creating a new platform to study podocyte biology with greater physiological relevance and second by applying this system to test the biophysical effects of altered mechanobiological signaling that may affect the progression of chronic kidney disease at the cellular level. 1